Department of Bioinformatics, Tongji University, Shanghai, China.
Digestive Diseases and Nutrition Center, Department of Pediatrics, The State University of New York at Buffalo, Buffalo, New York, USA.
J Pathol. 2016 Mar;238(4):531-42. doi: 10.1002/path.4650. Epub 2016 Jan 29.
Obese animals and non-alcoholic fatty liver disease (NAFLD) patients exhibit elevated blood alcohol, suggesting potential contributions of alcohol metabolism to the development of NAFLD. Liver gene expression in patients with biopsy-proven mild (N = 40) and severe (N = 32) NAFLD were compared to that in healthy liver donors (N = 7) and alcoholic hepatitis (AH; N = 15) using microarrays. Principal components analyses (PCA) revealed similar gene expression patterns between mild and severe NAFLD which clustered with those of AH but were distinct from those of healthy livers. Differential gene expression between NAFLD and healthy livers was consistent with established NAFLD-associated genes and NAFLD pathophysiology. Alcohol-metabolizing enzymes including ADH, ALDH, CYP2E1, and CAT were up-regulated in NAFLD livers. The expression level of alcohol-metabolizing genes in severe NAFLD was similar to that in AH. The NAFLD gene expression profiles provide new directions for future investigations to identify disease markers and targets for prevention and treatment, as well as to foster our understanding of NAFLD pathogenesis and pathophysiology. Particularly, increased expression of alcohol-metabolizing genes in NAFLD livers supports a role for endogenous alcohol metabolism in NAFLD pathology and provides further support for gut microbiome therapy in NAFLD management. Copyright © 2015 Pathological Society of Great Britain and Ireland. Published by John Wiley © Sons, Ltd.
肥胖动物和非酒精性脂肪性肝病 (NAFLD) 患者的血液酒精含量升高，表明酒精代谢可能对 NAFLD 的发展有一定的影响。采用微阵列技术比较了经活检证实的轻度（N=40）和重度（N=32）NAFLD 患者、健康供体肝脏（N=7）和酒精性肝炎（AH；N=15）的肝脏基因表达情况。主成分分析（PCA）显示，轻度和重度 NAFLD 的基因表达模式相似，与 AH 的基因表达模式聚类，但与健康肝脏的基因表达模式不同。NAFLD 与健康肝脏之间的差异基因表达与已建立的与 NAFLD 相关的基因和 NAFLD 病理生理学一致。NAFLD 肝脏中包括 ADH、ALDH、CYP2E1 和 CAT 在内的酒精代谢酶上调。严重 NAFLD 中酒精代谢基因的表达水平与 AH 相似。NAFLD 的基因表达谱为未来的研究提供了新的方向，以确定疾病标志物和预防治疗靶点，并促进我们对 NAFLD 发病机制和病理生理学的理解。特别是，NAFLD 肝脏中酒精代谢基因的表达增加支持内源性酒精代谢在 NAFLD 发病机制中的作用，并为 NAFLD 管理中的肠道微生物组治疗提供了进一步的支持。版权所有 © 2015 英国和爱尔兰病理学会。John Wiley & Sons，Ltd. 出版。
